Kaizo Kobayashi

Antithrombotic therapy with ticlopidine in chronic renal failure patients on maintenance hemodialysis -a multicenter collaborative double blind study-

Abstract The effect of a new inhibitor of platelet aggregation, ticlopidine, at a daily oral dose of 200mg, was investigated on prevention of thrombotic obstruction of the arterio-venous shunts or vascular grafts in 107 uremic patients under chronic hemodialysis: the patients were those who had suffered from frequent thrombotic episodes in their blood accesses. The study was conducted in a double blind fashion with an inactive placebo. Frequency of clot removal was significantly (p

Pattern of aliphatic dicarboxylic acids in uremic serum including a new organic acid, 2,4-dimethyladipic acid

(1) 2,4-Dimethyladipic acid was first identified in normal human urine using gas chromatography-mass spectrometry. Urinary excretion of 2,4-dimethyladipic acid in 7 healthy adults ranged from 4.9 mumol to 14 mumol per 24 h. (2) Succinic acid, adipic acid, 3-methyladipic acid, 2,4-dimethyladipic acid, pimelic acid and azelaic acid were identified in the ultrafiltrate of the blood obtained from a chronic uremic patient using a hemodialyzer. (3) Levels of succinic acid, adipic acid, 3-methyladipic acid, 2,4-dimethyladipic acid, pimelic acid and azelaic acid in uremic serum were determined using a mass fragmentographic technique. Concentration of succinic acid in uremic serum was comparable to that in normal serum, whereas concentrations of adipic acid, 3-methyladipic acid, 2,4-dimethyladipic acid, pimelic acid and azelaic acid were highly elevated in uremic serum.

Highly sulfated proteochondroitin sulfates synthesized in vitro by rat glomeruli

A previous report from this laboratory (Kobayashi, S., Oguri, K., Kobayashi, K. and Okayama, M. (1983) J. Biol. Chem. 258, 12051-12057) indicated that isolated rat glomeruli synthesized three species of sulfated glycoconjugates in vitro, namely, sulfated glycoproteins, proteoheparan sulfates and proteochondroitin sulfates. In the present study, the proteochondroitin sulfates, which showed the greatest incorporation of [35S]sulfate among the three sulfated glycoconjugates, were isolated and characterized. Radiolabeled tissue proteochondroitin sulfates were clearly separated on Sepharose CL-6B into three components with partition coefficients (Kd) of 0.16, 0.22 and 0.58, and medium proteochondroitin sulfates were separated into two components with Kd values of 0.33 and 0.62. When the chondroitin sulfate chains released by alkaline borohydride treatment were analyzed by digestion with chondroitinase AC-II, chondroitinase ABC, chondro-6-sulfatase and chondro-4-sulfatase, the results showed that all the samples contained glucuronosyl-N-acetylgalactosamine (chondroitinase AC-II-susceptible sequences, 72-86%) and iduronosyl-N-acetylgalactosamine (chondroitinase ABC-susceptible sequences, 14-28%), containing 4-sulfated N-acetylgalactosamine (50-70%) and 4,6-disulfated N-acetylgalactosamine (30-50%). On two-dimensional electrophoresis on cellulose acetate, all samples gave a single spot which closely coincided with chondroitin sulfate E of squid cartilage in electrophoretic mobility. These results indicated that the chains were highly sulfated chondroitin sulfates containing glucuronic acid and iduronic acid residues.

Profiling of uremic ultrafiltrate using high resolution gas chromatography-mass spectrometry - identification of 6 polyphenols.

An analytical method for separation and identification of compounds in uremic ultrafiltrate has been developed using a glass capillary column gas chromatography-mass spectrometry-computer system. The ultrafiltrate samples of blood were obtained during hemodialysis treatment of chronic uremic patients and non-uremic patients using the extracorporeal ultrafiltration method. Sample preparation consisted of acidification, extraction, evaporation, and trimethylsilylation. Many compounds were newly identified in the uremic ultrafiltrate by electron impact ionization, chemical ionization, and high resolution mass spectrometry. Six toxic polyphenols, namely, catechol, resorcinol, hydroquinone, 2-methoxyresorcinol, 3-methoxycatechol, and methoxyhydroquinone were first detected in the uremic ultrafiltrate.

Identification of some abnormal metabolites in psoriatic nail using gas chromatography—mass spectrometry

A gas chromatographic--mass spectrometric analysis was used to separate and identify abnormal compounds in the nail of psoriatic patients. The nail was extracted with heated ethanol, and the extract was analyzed with and without trimethylsilylation. Tetradecanoic acid octadecyl ester, hexadecanoic acid octadecyl ester and octadecanoic acid octadecyl ester were first identified in the psoriatic nail, but were not detected in normal nail.

Studies on LDH isozyme in human contracted kidney and in rabbit kidney after renal arterial stenosis

Abstract The LDH isozymes in human contracted kidney of chronic renal failure and in rabbit kidney after renal arterial stenosis have been studied. In the human contracted kidney, the cortical and medullary tissues showed considerably less LDH I and LDH II activity, compared with normal kidney. Similar results were found in rabbit kidney after unilateral renal arterial stenosis. In normal human and animal kidney, the cortical and medullary tissues exhibited strong LDH I and LDH II activity. In the papillary tissues, on the contrary, the activity of LDH IV and LDH V was high. These findings and animal experimental results suggest that in the contracted kidney where O 2 consumption is decreased, carbohydrate metabolism is mainly anaerobic.

Effects of 1α-OH-D3 on Bone Mineral Content in the Forearm of Chronic Hemodialyzed Patients

: The bone mineral content in the forearm of 99 male and 62 female patients who had never been treated with vitamin D on hemodialysis was measured to elucidate the relationship between bone mineral content and duration of hemodialysis. We found that reduction in bone mineral content related to the duration of hemodialysis in both sexes. 1--2 microgram/day of 1 alpha-OH-D3 was administered to 35 hemodialysis patients for 2 years. Bone mineral content in the forearm of both patient groups treated with and without 1 alpha-OH-D3 was measured every 3 months. Although bone mineral content in the forearm of the hemodialysis patients decreased, serum Ca, serum-ionized Ca, and serum phosphate levels increased and serum ALK-Pase and serum immunoreactive PTH decreased significantly after administration of 1 alpha-OH-D3. When bone mineral content in the forearm of patients treated with 1 alpha-OH-D3 was compared with that of untreated patients, the loss of bone mineral content in patients treated with 1 alpha-OH-D3 was less than that of the untreated group. In addition to uremic metabolic derangements, intermittently repeated humoral derangement on hemodialysis seems to cause loss of bone mineral content.

Studies on Nitrogen and Amino Acid Metabolism in Hemodialysis Patients Using 15N-Labelled Compounds1

The degree of 15N incorporation into serum albumin studied by 15N-urea administration in dialyzed patients on a 1.3 g/kg/day protein diet was shown to be almost the same as in non-dialyzed uremic patients on low protein diet, while there was no incorporation in a normal subject. 14.1 g of EAA and histidine was intravenously given in dialyzed patients on the high protein diet and improvements in the level of BUN and anemia were observed. The study with 15N-leucine in a patient proved that about 36% of EAA infused during dialysis was transferred into dialysate. AAD was prescribed by giving 15-20 g of EAA, histidine and tyrosine to patients at each dialysis. The AAD enabled us to give a large amount of EAA asymptomatically in a short time, improving anemia and decreasing the BUN level. 15N-glycine administration in a dialyzed patient proved that 15N incorporation into serum albumin was 3 times greater than his non-dialyzed uremic stage on a low protein diet, and that EAA serum concentrations and non-EAA which had not been added into dialysate were elevated.

Studies on Protein and Nitrogen Metabolism in Nephrotic Syndrome Using 15N-Labelled Glycine and Urea1

Administering 15N-labelled glycine, 15 N incorporation into serum albumin and its excretion into urine and feces, together with nitrogen balance were investigated in 3 nephrotic and 2 normal adults. Furthermore, 15N-labelled urea was injected into a nephrotic adult and a glomerulonephritic adult, both advanced in azotemia and treated on low protein diet, and a normal subject on a normal diet, to examine the amounts of 15N incorporation into serum albumin. In the 3 nephrotic patients whose nitrogen balance was almost maintained, incorporation of 15N-glycine into serum albumin has been proved greater than in the normal subjects. In any of the above patients, 15N excretion into urine was less than in the normal subjects. Fecal 15N excretion was 2.0--2.5 % of the doses, indicating that approximately 98 % of 15N-glycine was absorbed. In the nephrotic patients, 15N incorporation into serum albumin examined by 15N-labelled urea administration was more accelerated than in the glomerulonephritic patients and was negligible in the control subject on a normal diet.

CLINICAL STUDIES OF THE ELECTROCARDIOGRAM IN THE ENDSTADIUM OF CHRONIC RENAL FAILURE

慢性腎不全非代償期の心不全の原因を探る一つの検討方法として,腎不全死亡前約1週内の心電図変化をとり上げ,腎不全代償期群,心臓および腎臓が主病因と考えられない慢性疾患死亡患者群を対照として,それぞれの病態と心電図変化の関連を知ることにより,主として臨床検査成績を中心にして検討した.慢性腎不全代償期の心電図変化は,主として低蛋白,高血圧貧血などによるものであり,その程度は軽微であるのに対し,腎不全非代償期の変化は,上記因子の他,高Pi血,高K血などの高度の電解質異常および,種々なる異常代謝産物,さらには心包炎併発等により心筋障害を招来し,代償期の変化がいつそう増強せられ,ついに心不全に至ると結論せられる.